SLC26A2 p.Ser552=
c.1656A>G · rs753490868 · VCV2025124
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00119%, nfe)
Conditions
4
atelosteogenesis type II
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.24 | GERP -5.1, phastCons 0.029 |
| Overall | ||
| CADD | 4.476 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00119%
European (non-Finnish) · 14/1,180,008 alleles
Filtering AF
0.000688%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000539%
Overall
0.000958%
14/1,461,860 alleles · very rare
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- SLC26A2
- Protein
- p.Ser552=
- Coding
- c.1656A>G
- MANE Select
- NM_000112
- dbSNP
- rs753490868
- Type
- single nucleotide variant
- Location
- chr5:149981249 (GRCh38)
- Gene constraint
- LOEUF 1.091 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.97 · 4 PDB
- Residue 552
- a β-strand
Similar variants
- SLC26A2 p.Ser552Ter Pathogenic/Likely pathogenic ★★ same residue
- SLC26A2 p.Ser552Leu Uncertain significance ★ ⚠ same residue
- SLC26A2 c.700-1G>C Pathogenic/Likely pathogenic ★★ same condition
- SLC26A2 c.-26+2T>C Pathogenic ★★ same condition
- SLC26A2 p.Ala386Val Pathogenic/Likely pathogenic ★★ same condition
- SLC26A2 p.Ala715Val Pathogenic/Likely pathogenic ★★ same condition
- SLC26A2 p.Arg178Ter Pathogenic ★★ same condition
- SLC26A2 p.Arg279Trp Pathogenic/Likely pathogenic ★★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/slc26a2-p-ser552 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown